Abstract The relationship between early life adversity and increased stress-reactivity profiles later in life has been well established across species. Greater stress-reactivity increases vulnerability to pathologies including mood disorders such as depression. Developmental programming of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis appears to be a critical component mediating the interaction between early-life experience and later pathology. Greater adversity early in life typically results in a heightened LHPA tone. This interaction has been defined and characterized primarily by investigating physiological activation of the LHPA axis and resulting effects on behavior, hormones and neurobiology. However, life stressors or challenges typically do not arrive via purely physiological means. Stressors activate a cascade of responses which can serve to attenuate or exacerbate a given challenge. Cognitive, emotional and physiological activation all serve to both mediate and moderate response to a stressor. The prefrontal cortex (PFC) has emerged as a potential neuronal site where cognitive, emotional, and physiological signals converge to influence how an organism will uniquely respond to challenge. The PFC maintains a high level of plasticity well outside early developmental windows, unlike the LHPA. Little is known about the sensitivity of the PFC to adverse early experiences. While current early-experience research has focused on epigenetic regulation of hippocampal glucocorticoid receptors (GR) and HPA axis regulation little to no emphasis has been placed on regulation of PFC GRs. In this proposal we wish to assess how early-experience epigenetically mediates GR profiles at the level of the mPFC and how later exposure to stressor controllability paradigms might serve to alter these profiles. More specifically, how might systemic alterations in mPFC GR levels serve to alleviate some of the behavioural, cognitive, emotional and physiological symptoms of depression and chronic stress? This rat model will allow us to directly assess how disparities in parenting are causally related to differences in stress-reactivity at multiple levels (behavioral, hormonal and neurobiological). Moreover, by focusing on the developmental regulation of the PFC we can examine how social, affective and cognitive experiences converge to produce individual and population level differences in behavior and biology.